In sepsis the metabolic rate is accelerated and there is an accompanying increase in glucose and free fatty acid turnover and net protein catabolism. The hormonal signals which direct this metabolic response are poorly understood. In the present proposal I describe a septic dog model in which a hypermetabolic non lethal sepsis is produced. Following characterization of the model both metabolically and hemodynamically, the role glucagon plays in directing hepatic glucose metabolism will be examined by looking at the effect its acute removal has on hepatic glucose metabolism. In the second series of experiments, the gluconeogenic potential of the liver will be assessed by looking at the ability of the liver to respond to an increment in glucagon concentration. The third protocol will examine the effect of hyperglycemia and hyperinsulinemia on hepatic and peripheral glucose metabolism in the septic dog. The goal of these studies to define how hormonal signals play a role in directing the metabolic response to sepsis.